Differential expression profiles of Streptococcus mutans ftf, gtf and vicR genes in the presence of dietary carbohydrates at early and late exponential growth phases

Shemesh, Moshe; Tam, Avshalom; Feldman, Mark; Steinberg, Doron

doi:10.1016/j.carres.2006.05.010

Cited by 65 publications

(67 citation statements)

References 34 publications

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“…Recently, it was shown that vicR and gtfB/C were regulated differentially depending on the bacterial growth phase (i.e., early exponential versus late exponential), as well as the type of sugar added to the culture medium (e.g., glucose, sucrose, fructose, mannitol, sorbitol, etc.) (34). The researchers showed that the type of carbohydrate added during growth had a significant influence on the expression of the gtf genes, whereas the vicR expression was more dependent on the growth phase than on the carbohydrate source.…”

Section: Discussionmentioning

confidence: 99%

The Streptococcus mutans vicX Gene Product Modulates gtfB / C Expression, Biofilm Formation, Genetic Competence, and Oxidative Stress Tolerance

et al. 2007

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Streptococcus mutans is considered one of the primary etiologic agents of dental caries. Previously, we characterized the VicRK two-component signal transduction system, which regulates multiple virulence factors of S. mutans. In this study, we focused on the vicX gene of the vicRKX tricistronic operon. To characterize vicX, we constructed a nonpolar deletion mutation in the vicX coding region in S. mutans UA159. The growth kinetics of the mutant (designated SmuvicX) showed that the doubling time was longer and that there was considerable sensitivity to paraquat-induced oxidative stress. Supplementing a culture of the wild-type UA159 strain with paraquat significantly increased the expression of vicX (P < 0.05, as determined by analysis of variance [ANOVA]), confirming the role of this gene in oxidative stress tolerance in S. mutans. Examination of mutant biofilms revealed architecturally altered cell clusters that were seemingly denser than the wild-type cell clusters. Interestingly, vicX-deficient cells grown in a glucose-supplemented medium exhibited significantly increased glucosyltransferase B/C (gtfB/C) expression compared with the expression in the wild type (P < 0.05, as determined by ANOVA). Moreover, a sucrose-dependent adhesion assay performed using an S. mutans GS5-derived vicX null mutant demonstrated that the adhesiveness of this mutant was enhanced compared with that of the parent strain and isogenic mutants of the parent strain lacking gtfB and/or gtfC. Also, disruption of vicX reduced the genetic transformability of the mutant approximately 10-fold compared with that of the parent strain (P < 0.05, as determined by ANOVA). Collectively, these findings provide insight into important phenotypes controlled by the vicX gene product that can impact S. mutans pathogenicity.

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Section: Discussionmentioning

confidence: 99%

The Streptococcus mutans vicX Gene Product Modulates gtfB / C Expression, Biofilm Formation, Genetic Competence, and Oxidative Stress Tolerance

et al. 2007

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“…In S. mutans, CcpA does play an important role in the global control of gene expression (26), but CcpA-independent mechanisms involving the PTS phosphocarrier protein HPr and various EII permeases play dominant roles in CCR, regulating catabolic pathways such as the fruAB operon, the fructose/mannose-PTS encoded by levDEFG (22,27), and transport and catabolism of cellobiose (28) and lactose (29). There are data to support that sucrose may be a preferred carbohydrate source that can elicit CCR in S. mutans (30)(31)(32)(33). For example, a microarray-based transcriptomic analysis (30) indicated that growth in sucrose resulted in 2-to 3-fold-lower expression of the maltose/maltodextrin ABC transporter (SMU1568 to SMU1571) and the msm operon.…”

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confidence: 99%

Comprehensive Mutational Analysis of Sucrose-Metabolizing Pathways in Streptococcus mutans Reveals Novel Roles for the Sucrose Phosphotransferase System Permease

Zeng

Burne

2012

Journal of Bacteriology

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Sucrose is perhaps the most efficient carbohydrate for the promotion of dental caries in humans, and the primary caries pathogen Streptococcus mutans encodes multiple enzymes involved in the metabolism of this disaccharide. Here, we engineered a series of mutants lacking individual or combinations of sucrolytic pathways to understand the control of sucrose catabolism and to determine whether as-yet-undisclosed pathways for sucrose utilization were present in S. mutans. Growth phenotypes indicated that gtfBCD (encoding glucan exopolysaccharide synthases), ftf (encoding the fructan exopolysaccharide synthase), and the scrAB pathway (sugar-phosphotransferase system [PTS] permease and sucrose-6-PO 4 hydrolase) constitute the majority of the sucrose-catabolizing activity; however, mutations in any one of these genes alone did not affect planktonic growth on sucrose. The multiple-sugar metabolism pathway (msm) contributed minimally to growth on sucrose. Notably, a mutant lacking gtfBC, which cannot produce water-insoluble glucan, displayed improved planktonic growth on sucrose. Meanwhile, loss of scrA led to growth stimulation on fructooligosaccharides, due in large part to increased expression of the fruAB (fructanase) operon. Using the LevQRST four-component signal transduction system as a model for carbohydrate-dependent gene expression in strains lacking extracellular sucrases, a PlevD-cat (EIIA Lev ) reporter was activated by pulsing with sucrose. Interestingly, ScrA was required for activation of levD expression by sucrose through components of the LevQRST complex, but not for activation by the cognate LevQRST sugars fructose or mannose. Sucrose-dependent catabolite repression was also evident in strains containing an intact sucrose PTS. Collectively, these results reveal a novel regulatory circuitry for the control of sucrose catabolism, with a central role for ScrA. Sucrose is among the most cariogenic carbohydrates (1, 2), and this disaccharide, composed of ␤2,1-linked fructose and glucose, influences the development of caries in multiple ways. First, sucrose can serve as a readily metabolizable carbon and energy source for many members of the oral microbiome and is a particularly effective substrate for generation of organic acids via glycolysis by the abundant oral streptococci and Actinomyces spp. that comprise a large proportion of the oral microbiome. Many oral bacteria possess transport systems for sucrose but can also hydrolyze sucrose outside the cell. Sucrose is a substrate for a variety of glucosyltransferase enzymes (GTFs) that are secreted mainly by oral streptococci. For example, the GTF enzymes of Streptococcus mutans, the primary etiologic agent of human dental caries, release free fructose and form high-molecular-mass ␣1,3-and ␣1,6-linked homopolymers of glucose, commonly called glucans or mutan, which act as an adhesive scaffolding to promote the formation of oral biofilms, particularly on the smooth surfaces of the teeth (3, 4). Many oral streptococci and certain Actinomyces spp. also produc...

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“…The YycFG system appears to be essential for growth in most bacterial species that encode it (10,17,27,48). The essentiality may be linked to its control of murein biosynthesis (1,3,6,7,21,26,32,33), cell division (10,12,21), lipid integrity (3,27,29,33), exopolysaccharide biosynthesis and biofilm formation (1,2,6,39,41), and virulence factor expression (2,6,24,26,33,39). Because of these effects on essential functions and the fact that the YycFG TCS is widely conserved in low-GC gram-positive bacteria, including several major pathogens, it has been considered a potential target for anti-infective therapeutics (see, e.g., references 14, 25, 35-37, and 42).…”

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confidence: 99%

“…In B. subtilis, YycJ does not seem to be tied to YycFG TCS signaling (45), whereas the VicX protein does seem to play some unspecified role in signaling through the VicRK TCS in species of Streptococcus (32,40). Considerably more is known about the function and structures of the YycH and YycI proteins, which are membrane bound and contain extracellular domains (41)(42)(43) (Fig. 1).…”

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confidence: 99%

Essentiality, Bypass, and Targeting of the YycFG (VicRK) Two-Component Regulatory System in Gram-Positive Bacteria

Winkler

Hoch

2008

J Bacteriol

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Differential expression profiles of Streptococcus mutans ftf, gtf and vicR genes in the presence of dietary carbohydrates at early and late exponential growth phases

Cited by 65 publications

References 34 publications

The Streptococcus mutans vicX Gene Product Modulates gtfB / C Expression, Biofilm Formation, Genetic Competence, and Oxidative Stress Tolerance

The Streptococcus mutans vicX Gene Product Modulates gtfB / C Expression, Biofilm Formation, Genetic Competence, and Oxidative Stress Tolerance

Comprehensive Mutational Analysis of Sucrose-Metabolizing Pathways in Streptococcus mutans Reveals Novel Roles for the Sucrose Phosphotransferase System Permease

Essentiality, Bypass, and Targeting of the YycFG (VicRK) Two-Component Regulatory System in Gram-Positive Bacteria

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